ReGen Biologics (Franklin Lakes, New Jersey) has obtained CE marketing approval for its Collagen Meniscus Implant (CMI) product following positive results of a European multicenter clinical study. The study established the efficacy of the CMI device in providing significant improvement in pain and function in patients with knee meniscal damage.
"CMI is the first tissue-engineered meniscus repair product to receive CE marking," said Gerald Bisbee Jr., chairman and CEO at ReGen. He anticipates completion of patient enrollment in the first U.S. multicenter clinical trial by year-end. Enrollment in the second clinical trial is due to begin in the third quarter.
The CMI, which is a resorbable collagen scaffold sutured into place to support regeneration of meniscal tissue, will be marketed in Europe in partnership with Sulzer Medica (Winterthur, Switzerland). It is used in the treatment of tears of the meniscus of the knee, the most frequently damaged cartilage in the human body.
Separately, the Robodoc surgical assistant made by Integrated Surgical Systems (Davis, California) is to be used for the first time for a total knee replacement procedure during May at the Berufsgenossenschaftliche Unfallklinik (BGU; Frankfurt, Germany). Robodoc already is used at the BGU clinic for hip replacement surgery, but total knee replacement requires a higher level of accuracy.
Another CE marking has been reported by Ascension Orthopedics (Austin, Texas) for its metacarpophalangeal (MP) endoprosthesis, developed in collaboration with the Mayo Clinic (Rochester, Minnesota). The Ascension MP implant, which has already been used effectively in Britain and Spain, is fabricated from pyrolytic carbon, which has long been used in mechanical heart valves, but not previously in joint reconstruction applications, according to Jerome Klawitter, president of the company.
Although the device has limitations in use, depending on associated soft-tissue damage and the level of cubital deformity, it is expected to be most effective in rheumatoid arthritis and osteoarthritis cases. Dr. Mario de Campo Martinez, head of the hand surgery team at the Ramon y Cajal Hospital (Madrid, Spain), where the device is the subject of a five-year efficacy trial, expects the trials to generate evidence of a lifetime in excess of 20 years.
Klawitter said the company plans a range of hand, foot and elbow small joint implants. He expects the small-joint replacement market to be boosted by relatively low costs compared to the high cost of treating arthritis-related disease with anti-inflammatory drugs and corticosteroids.
Sulzer/Tutogen spinal fusion deal
Sulzer Medica is to pay Tutogen Medical (Erlangen, Germany) $3 million over two years for world exclusive rights to the Tutoplast human bone tissue products for spinal applications. The two companies also will collaborate on the development of a range of proprietary tissue products and implants. Sulzer Medica will market the products in conjunction with its BAK and Proximity spinal fusion cages.
The Tutoplast processed allograft bone product helps to stabilize the vertebrae, as well as providing a structural support for the growth of new bone which will fuse the vertebrae together.
Controlled-release bone cements
Controlled release of antimicrobial substances from bone cement via matrix bonding is a cost-effective and clinically established method of preventing deep infection in patients undergoing total hip replacement procedures. E. Merck's (Darmstadt, Germany) Palacos and Septopal methyl-methacrylate cements with gentamicin are widely used in Europe to reduce or prevent revisions in hip replacements.
Merck scientists are carrying out clinical investigations into the use of antineoplastic methotrexate-releasing bone cement following tumor excision. Investigations into a coating for endoprostheses that contains osteo-inductive peptides for improved device-bone integration have reached the preclinical stage.
DEXA/laser bone mineral scanning
Demetech (Norrkoping, Sweden) has launched in Europe its Calscan Dexa-t bone mineral scanning system which measures bone mass density in the calcaneus by combining dual energy X-ray absorptiometry (DEXA) with laser measurement of the heel thickness. The company claims measurement data accuracy of better than +/-2%, with only 35 seconds needed from measurement to finished report.
Aloka (Tokyo) has placed on general release two bone densitometers. The DCS-600EX uses advanced DXA technology to scan rapidly the forearm of the patient, and is particularly suitable for cost-effective multiple examinations. The Aloka AOS-100 ultrasound osteo screener is proposed for pregnant women and young children, since it emits no ionizing radiation. The portable Pegasus ultrasound sonometer for osteoporosis screening from Osteomed (Nice, France) includes a built-in microcomputer said to allow for an accurate diagnosis from a heel scan to be provided in 40 seconds.
Hologic's (Bedford, Massachusetts) Delphi QDR DXA bone densitometer has been developed to identify simultaneously existing vertebral fractures and low bone density commonly encountered in women over the age of 50. The system, which can capture the entire spine in a single image, also is suitable for normal bone mineral density measurements.
Cancer trials update
The giant United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), just launched, will run for 10 years, screening 200,000 postmenopausal women aged 50 to 74 and will cost an estimated $35 million. The trial is intended to help in decisions as to whether a national screening program should be introduced, based on the life-saving potential of early diagnosis and its cost-effectiveness.
Participants in the trial will be allocated to either annual screening over six years or to follow-up without screening. Those screened will receive either a transvaginal ultrasound scan or a CA-125 tumor marker blood test. The trials will be held at 12 regional screening centers coordinated by Professor Ian Jacobs at St. Bartholomew's Hospital (London). Currently, 70% of patients with diagnosed cases die within five years, while 90% of early diagnosis cases survive. The aim of the trial is to halve ovarian cancer mortality in Britain from a current 5,000 per year, with 6,000 new diagnosed cases.
Jacobs has emphasized that the aim of the trial is not to improve screening by cross-referencing more than one marker, but to interpret at a more sophisticated level CA-125 results based on an assessment of risk in relation to varying blood CA-125 levels encountered over time. He said that future investigations could include research into mutations of BRCA1 and BRCA2 genes which appear to predispose toward both breast and ovarian cancers.
A 15-year study of more than 5,000 women in the UK has shown that the removal of benign ovarian cysts may not reduce the risks of a woman dying of ovarian cancer.
The trial, results of which were published in the March 25 issue of The Lancet, showed that the removal of persistent ovarian cysts was not associated with a decrease in the number of expected deaths from ovarian cancer compared to other cancers.
Timothy Crayford and his group from King's College Hospital (London) said, "We hope that our study will now encourage further debate about the viability of screening for ovarian cancer and what to do with women who have cysts discovered on their ovaries at a routine ultrasound examination." He added that recent advances in ultrasound technology now allow physicians to distinguish between benign and malignant cysts more precisely. He said that the trial findings supported leaving cysts in place if they are identified as benign.
Photoelectron's (Lexington, Massachusetts) Photon Radiosurgery System (PRS) is to be used in a clinical trial starting shortly at the Middlesex Hospital (London). The trial will evaluate whether a single intra-operative treatment for breast cancer can effectively replace the conventional six weeks of external beam radiation therapy. The RPS system will be used immediately after surgical removal of the tumor to deliver a single dose of intense, low-energy radiation to the inside of the tumor cavity. Photoelectron expects that additional European and U.S. centers also will participate in the trial.
The Internet and clinical trials
British Telecom (BT; London), the UK privatized telephone service provider, plans to become a major player in drug research support services with the launch of BT Clinical Trials Services. The new service will connect all those involved in a clinical trial via a high-security community extranet. For the first time, drug and device companies will be able to tap the resources of a linked international community of clinical investigators
According to Chris Moore, a director at PriceWaterhouse Coopers, adoption of BT's service could offer cost savings of 10% to 15% for typical Phase III trials. With drug companies running an average of 45 Phase III trials each year, this could amount to annual savings of $35 million to $50 million. "A single trial as part of BT's pilot showcase service would be cost-neutral and there would be huge savings in multiple trials," Moore said.
GPs and clinical trials
Although the European Commission has produced a draft directive to harmonize rules governing the conduct of clinical trials throughout the European Union (EU), there are at present many differences in national rules.
For example, of the 15 countries in the EU, four – Italy, Portugal, Greece, and Austria – do not allow general practitioners (GPs) to take part in Phase III trials. In the case of Greece and Italy, Phase III trials can only be conducted by physicians within a hospital or university location.
Outside the EU, general practitioners again cannot take part in Phase III trials in Slovenia, Turkey, South Korea, and Panama.
The Italian Health Ministry is looking at whether GPs' involvement in clinical trials should be extended to Phase III. In principle, they can take part in Phase IV trials, but in practice this has to be agreed upon on a case-by-case basis by the Health Ministry.
Shock wave therapy
Healthtronics' (Marietta, Georgia) OssaTron shock wave therapy device has successfully been used in a clinical trial in Austria for the treatment of non-unions, or delayed-healing fractures. The study indicated that a single application of shock waves stimulates new bone formation, justifying its use in delayed fracture or non-union problems.
In the study, Wolfgang Schaden of the Unfallkrankenhaus Meidling (Vienna, Austria) treated 97 fractures with a single shock wave exposure. Of those, 63 were shaft fractures in long bones and 34 were fractures in cancellous bone. Union was achieved within six months in 71 of the patients (73%), confirmed by X-ray or CT imaging to assess bony consolidation. Roy Brown, president of Healthtronics, said pivotal Phase I trials in the U.S. to assess OssaTron shock wave therapy in non-unions have been completed, with Phase II trials due to start shortly.
Uroplasty incontinence implant for Europe
Uroplasty (Minneapolis, Minnesota) has received CE marking clearance for the Macroplastique soft tissue bulking material. The Macroplastique implantation system is designed for minimally invasive treatment of female stress incontinence without the need for endoscopy, according to the company. Macroplastique also is used for treating male incontinence resulting from prostate surgery and vesicouretheral reflux. The European market for urinary sphincter augmentation products is estimated at around $18 million, of which half is in artificial sphincters – mostly from American Medical Systems (Minnetonka, Minnesota) – and the balance in augmentation injectables like collagen, silicone and Teflon paste.
FDA to name assessment bodies
The FDA has completed the first two of three audit steps with at least three European notified bodies as conformity assessment bodies (CABs) under the Mutual Recognition Agreement between Europe and the U.S. Front-runners for FDA approval are understood to include one candidate CAB each from Britain, Denmark, and Germany. The European Union is well behind the FDA and has not yet even started to designate candidate CABs in the U.S.
Separately, the FDA has issued a warning letter to ERBE Elektromedizin (Tubingen, Germany) following a factory inspection last October. The letter cited allegations of misbranding and new applications, as well as problems with manufacturing and storage outside good manufacturing practices.
Drug industry worries about EU enlargement
As the former communist countries of central and eastern Europe line up to join the European Union, and as the front-runners like Poland and Hungary get closer to the finishing line, the European pharmaceutical industry is becoming increasingly concerned about decreasing profits and patent coverage.
Their particular worries, which are mirrored by similar concerns from Europe's medical device manufacturers, are about laxity in the implementation of intellectual property rights in new member states and the prospect of massive parallel importing from poorer member states into Germany or the UK.
The European Federation of Pharmaceutical Industries and Associations (EFPIA; Brussels, Belgium) has proposed that there be restrictions on the free movement of pharmaceuticals (and medical devices) for all products covered by patents in the existing 15 member states but not in acceding countries.
The European Commission's position is that it expects applicant countries to have put into force all of the commission's rules in respect to the EU internal market before they join. It remains to be seen how responsive it will be to industry's calls to impose transition provisions that would effectively split the single market.
Cuts may lead to rationing
Plans by the German government to keep spending down in the health care system during 2000 will continue the pressures encountered during 1999, where reimbursement cuts have already produced adverse effects on medical device and diagnostic markets.
In January 1999, hospital reimbursements for 72 diagnosis-related groups (DRGs) and 147 procedures were redefined or reduced. Cardiac and orthopedic surgery were hardest hit, with cardiac surgery down by as much as 22% and cardiac DRGs by 23%. Hip replacement procedure reimbursements went down by 12% and knee implants by 25%.
Outpatient fee reimbursements also were reduced in many cases as of last April, and special laboratory tests as of July. As a result, numbers of "special laboratory tests" (those not carried out in the physician's office) fell by 36% in July/August 1999 compared to the previous year. Fees paid to laboratory physicians fell even more precipitously by 46% over the same period. German diagnostic companies producing these "special tests" reported a drop in sales last year of up to 25% as a result.
It seems likely that austerity measures imposed by German health care policymakers have reached their limits. The continuation of present spending limits in essential areas of health care will inevitably lead to rationing of resources. This will be of little benefit to patients, health care providers or the medical device industry.